Co-targeting of glial activation and inflammation by tsRNA-Gln-i-0095 for treating retinal ischemic pathologies
Abstract Ischemic retinopathies are the major causes of blindness, yet effective early-stage treatments remain limited due to an incomplete understanding of the underlying molecular mechanisms. Significant changes in gene expression often precede structural and functional alterations. Transfer RNA (...
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Main Authors: | , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
BMC
2025-01-01
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Series: | Cell Communication and Signaling |
Subjects: | |
Online Access: | https://doi.org/10.1186/s12964-024-02013-x |
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Summary: | Abstract Ischemic retinopathies are the major causes of blindness, yet effective early-stage treatments remain limited due to an incomplete understanding of the underlying molecular mechanisms. Significant changes in gene expression often precede structural and functional alterations. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are emerging as novel gene regulators, involved in various biological processes and human diseases. In this study, tsRNA-Gln-i-0095 was identified as a novel regulator, which was significantly upregulated in retinal ischemia/reperfusion (I/R) injury. Reducing the levels of tsRNA-Gln-i-0095 suppressed reactive gliosis, lowered inflammatory cytokine levels, and protected retinal ganglion cells from I/R injury. These effects led to reduced structural and functional damage, inhibited glial activation and inflammation, and enhanced neuronal function. Mechanistically, tsRNA-Gln-i-0095 downregulated the expression of NFIA and TGFBR2 through a miRNA-like mechanism. Collectively, this study highlights the potential of targeting tsRNA-Gln-i-0095 as a novel therapeutic approach to reduce retinal I/R injury and preserve visual function. Graphical abstract |
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ISSN: | 1478-811X |